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https://www.readbyqxmd.com/read/29152652/effect-of-wnt1-and-wnt5a-on-the-development-of-dopaminergic-neurons-and-toxicity-induced-by-combined-exposure-to-paraquat-and-maneb-during-gestation-and-lactation
#1
Jing Ma, Cui Huang, Kun Ma, Yan-Ping Wu, Bai-Xiang Li, Yan Sun
Paraquat (PQ) and maneb (MB) are widely used herbicides. Wingless (Wnt) proteins serve a role in the development and differentiation of dopaminergic neurons. Previous studies demonstrated that combined exposure to PQ and MB damages dopaminergic neurons in the midbrain. Effects of PQ and MB exposure on midbrain Wnt proteins have also been previously reported. In the present study, from the 5th day of gestation to weaning of the offspring, pregnant Sprague‑Dawley rats were administrated saline, or PQ and MB at two different doses: high, 15 mg/kg body weight PQ + 45 mg/kg body weight MB; or low, 10 mg/kg body weight PQ + 30 mg/kg body weight MB...
October 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29147905/transcriptional-regulation-of-dj-1
#2
Kazuko Takahashi-Niki, Takeshi Niki, Sanae M M Iguchi-Ariga, Hiroyoshi Ariga
DJ-1 is an oncogene and also a causative gene for familial Parkinson's disease. DJ-1 has various functions, and the oxidative status of a cysteine residue at position 106 (C106) is crucial for determination of the activation level of DJ-1.DJ-1 binds to many proteins, including various transcription factors, and acts as a coactivator or corepressor for regulating their target genes without direct binding to DNA, thereby affecting various cell functions. DJ-1-regulating transcription factors and their modified proteins are the androgen receptor and its regulatory proteins, p53; polypyrimidine tract-binding protein-associated splicing factor (PSF); Keap1, an inhibitor for nuclear factor erythroid2-related factor 2 (Nrf2); sterol regulatory element-binding protein (SREBP); Ras-responsive element-binding protein (RREB1); signal transducer and activator of transcription 1 (STAT1); and Nurr1...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29145474/long-3-utr-of-nurr1-mrnas-is-targeted-by-mirnas-in-mesencephalic-dopamine-neurons
#3
Luis Alberto Pereira, Roberto Munita, Marcela Paz González, María Estela Andrés
The development of mesencephalic dopamine neurons and their survival later in life requires the continuous presence of the transcription factor Nurr1 (NR4A2). Nurr1 belongs to the nuclear receptors superfamily. However, it is an orphan member that does not require a ligand to regulate the transcription of its target genes. Therefore, controlling the expression of Nurr1 is an important manner to control its function. Several reports have shown that microRNAs (miRNAs) regulate Nurr1 expression. However, Nurr1 has several splicing variants, posing the question what variants are subjected to miRNA regulation...
2017: PloS One
https://www.readbyqxmd.com/read/29115391/effect-on-the-dopaminergic-metabolism-induced-by-oral-exposure-to-simazine-during-the-prepubertal-period-in-rats
#4
Xueting Li, Jia Yu, Yanping Wu, Baixiang Li
The herbicide simazine is widely used in agricultural and non-agricultural fields. Studies have shown that simazine inhibits the proliferation of dopaminergic cells and affects the developmental differentiation of dopamine neurons. However, little is known about the effects of simazine on dopaminergic metabolism. Therefore, the present study examined the effects of simazine on Sprague‑Dawley (SD) rats from weaning to puberty (40 days exposure). Simazine was administered orally to SD rats at doses of 0, 12...
October 20, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29042395/nuclear-receptor-profiling-in-prostatospheroids-and-castration-resistant-prostate-cancer
#5
Zhu Wang, Dinglan Wu, Chi-Fai Ng, Jeremy Yuen-Chun Teoh, Shan Yu, Yuliang Wang, Franky Leung Chan
Nuclear receptors (NRs), which belong to a superfamily of transcription factors and consist of a total of 48 members in humans, govern the expression of genes involved in a board range of developmental, reproductive, metabolic and immunological programs. Given the significant importance of androgen receptor and a few known NRs in the progression of prostate cancer, we surveyed the expression profiles of the entire NR superfamily in three-dimensional (3D) cultured prostatospheroids derived from different prostate cancer cell lines and a tumor xenograft model of castration-resistant prostate cancer VCaP-CRPC by quantitative real-time RT-PCR...
October 17, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28989991/region-specific-effects-of-aging-and-the-nurr1-null-heterozygous-genotype-on-dopamine-neurotransmission
#6
Evangel Kummari, Shirley Guo-Ross, Jeffrey B Eells
The transcription factor Nurr1 is essential for dopamine neuron differentiation and is important in maintaining dopamine synthesis and neurotransmission in the adult. Reduced Nurr1 function, due to the Nurr1-null heterozygous genotype (+/-), impacts dopamine neuron function in a region specific manner resulting in a decrease in dopamine synthesis in the dorsal and ventral striatum and a decrease in tissue dopamine levels in the ventral striatum. Additionally, maintenance of tissue dopamine levels in the dorsal striatum and survival of nigrostriatal dopamine neurons with aging (>15 months) or after various toxicant treatments are impaired...
June 2017: Neurochem Neuropharmacol
https://www.readbyqxmd.com/read/28943456/permethrin-pesticide-induces-nurr1-up-regulation-in-dopaminergic-cell-line-is-the-pro-oxidant-effect-involved-in-toxicant-neuronal-damage
#7
Laura Bordoni, Donatella Fedeli, Cinzia Nasuti, Melania Capitani, Dennis Fiorini, Rosita Gabbianelli
The mechanisms associated to the development of neurodegeneration due to pesticide exposure are not clear yet. In this study we evaluated how permethrin pesticide (PERM) can influence the Nurr1 gene and protein expression, and if a pro-oxidant activity of the pesticide contributes to up-regulation of Nurr1 in a dopaminergic cell line. Incubation of PC12 cells with 1μM PERM for 72h, leads to over expression of Nurr1 gene. This effect occurs with both corn oil and extra virgin olive oil (EVO) used to solubilize the toxicant...
September 22, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/28904869/high-glucose-stimulates-expression-of-aldosterone-synthase-cyp11b2-and-secretion-of-aldosterone-in-human-adrenal-cells
#8
Hiroki Shimada, Naotaka Kogure, Erika Noro, Masataka Kudo, Kaori Sugawara, Ikuko Sato, Kyoko Shimizu, Makoto Kobayashi, Dai Suzuki, Rehana Parvin, Takako Saito-Ito, Akira Uruno, Akiko Saito-Hakoda, William E Rainey, Sadayoshi Ito, Atsushi Yokoyama, Akira Sugawara
Aldosterone synthase is the key rate-limiting enzyme in adrenal aldosterone production, and induction of its gene (CYP11B2) results in the progression of hypertension. As hypertension is a frequent complication among patients with diabetes, we set out to elucidate the link between diabetes mellitus and hypertension. We examined the effects of high glucose on CYP11B2 expression and aldosterone production using human adrenal H295R cells and a stable H295R cell line expressing a CYP11B2 5'-flanking region/luciferase cDNA chimeric construct...
September 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28878618/the-non-survival-effects-of-glial-cell-line-derived-neurotrophic-factor-on-neural-cells
#9
REVIEW
Daniel Cortés, Oscar A Carballo-Molina, María José Castellanos-Montiel, Iván Velasco
Glial cell line-derived neurotrophic factor (GDNF) was first characterized as a survival-promoting molecule for dopaminergic neurons (DANs). Afterwards, other cells were also discovered to respond to GDNF not only as a survival factor but also as a protein supporting other cellular functions, such as proliferation, differentiation, maturation, neurite outgrowth and other phenomena that have been less studied than survival and are now more extendedly described here in this review article. During development, GDNF favors the commitment of neural precursors towards dopaminergic, motor, enteric and adrenal neurons; in addition, it enhances the axonal growth of some of these neurons...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28844658/direct-reprogramming-of-resident-ng2-glia-into-neurons-with-properties-of-fast-spiking-parvalbumin-containing-interneurons
#10
Maria Pereira, Marcella Birtele, Shelby Shrigley, Julio Aguila Benitez, Eva Hedlund, Malin Parmar, Daniella Rylander Ottosson
Converting resident glia into functional and subtype-specific neurons in vivo by delivering reprogramming genes directly to the brain provides a step forward toward the possibility of treating brain injuries or diseases. To date, it has been possible to obtain GABAergic and glutamatergic neurons via in vivo conversion, but the precise phenotype of these cells has not yet been analyzed in detail. Here, we show that neurons reprogrammed using Ascl1, Lmx1a, and Nurr1 functionally mature and integrate into existing brain circuitry and that the majority of the reprogrammed neurons have properties of fast-spiking, parvalbumin-containing interneurons...
September 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28800627/suppressive-effects-of-rxr-agonist-pa024-on-adrenal-cyp11b2-expression-aldosterone-secretion-and-blood-pressure
#11
Dai Suzuki, Akiko Saito-Hakoda, Ryo Ito, Kyoko Shimizu, Rehana Parvin, Hiroki Shimada, Erika Noro, Susumu Suzuki, Ikuma Fujiwara, Hiroyuki Kagechika, William E Rainey, Shigeo Kure, Sadayoshi Ito, Atsushi Yokoyama, Akira Sugawara
The effects of retinoids on adrenal aldosterone synthase gene (CYP11B2) expression and aldosterone secretion are still unknown. We therefore examined the effects of nuclear retinoid X receptor (RXR) pan-agonist PA024 on CYP11B2 expression, aldosterone secretion and blood pressure, to elucidate its potential as a novel anti-hypertensive drug. We demonstrated that PA024 significantly suppressed angiotensin II (Ang II)-induced CYP11B2 mRNA expression, promoter activity and aldosterone secretion in human adrenocortical H295R cells...
2017: PloS One
https://www.readbyqxmd.com/read/28800615/pitx3-and-en1-determine-the-size-and-molecular-programming-of-the-dopaminergic-neuronal-pool
#12
Willemieke M Kouwenhoven, Lars von Oerthel, Marten P Smidt
Mesodiencephalic dopaminergic (mdDA) neurons are located in the ventral midbrain. These neurons form the substantia nigra (SNc) and the ventral tegmental area (VTA). Two transcription factors that play important roles in the process of terminal differentiation and subset-specification of mdDA neurons, are paired-like homeodomain transcription factor 3 (Pitx3), and homeobox transcription factor Engrailed 1 (En1). We previously investigated the single Pitx3KO and En1KO and observed important changes in the survival of mdDA neurons of the SNc and VTA as well as altered expression of pivotal rostral- and caudal-markers, Ahd2 and Cck, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28798667/the-foxp2-driven-network-in-developmental-disorders-and-neurodegeneration
#13
Franz Oswald, Patricia Klöble, André Ruland, David Rosenkranz, Bastian Hinz, Falk Butter, Sanja Ramljak, Ulrich Zechner, Holger Herlyn
The transcription repressor FOXP2 is a crucial player in nervous system evolution and development of humans and songbirds. In order to provide an additional insight into its functional role we compared target gene expression levels between human neuroblastoma cells (SH-SY5Y) stably overexpressing FOXP2 cDNA of either humans or the common chimpanzee, Rhesus monkey, and marmoset, respectively. RNA-seq led to identification of 27 genes with differential regulation under the control of human FOXP2, which were previously reported to have FOXP2-driven and/or songbird song-related expression regulation...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28769982/nurr1-downregulation-favors-osteoblastic-differentiation-of-mscs
#14
Adriana Di Benedetto, Francesca Posa, Claudia Carbone, Stefania Cantore, Giacomina Brunetti, Matteo Centonze, Maria Grano, Lorenzo Lo Muzio, Elisabetta A Cavalcanti-Adam, Giorgio Mori
Mesenchymal stem cells (MSCs) have been identified in human dental tissues. Dental pulp stem cells (DPSCs) were classified within MSC family, are multipotent, can be isolated from adult teeth, and have been shown to differentiate, under particular conditions, into various cell types including osteoblasts. In this work, we investigated how the differentiation process of DPSCs toward osteoblasts is controlled. Recent literature data attributed to the nuclear receptor related 1 (NURR1), a still unclarified role in osteoblast differentiation, while NURR1 is primarily involved in dopaminergic neuron differentiation and activity...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28746897/parkinsonian-features-in-aging-gfap-hmox1-transgenic-mice-overexpressing-human-ho-1-in-the-astroglial-compartment
#15
Wei Song, Marisa Cressatti, Hillel Zukor, Adrienne Liberman, Carmela Galindez, Hyman M Schipper
Epigenetic influences mediating brain iron deposition, oxidative mitochondrial injury, and macroautophagy in Parkinson disease and related conditions remain enigmatic. Here, we show that selective overexpression of the stress protein, heme oxygenase-1 (HO-1) in astrocytes of GFAP.HMOX1 transgenic mice between 8.5 and 19 months of age results in nigrostriatal hypodopaminergia associated with locomotor incoordination and stereotypy; downregulation of tyrosine hydroxylase, DAT, LMX1B, Nurr1, Pitx3 and DJ-1 mRNA and/or protein; overproduction of α-synuclein and ubiquitin; oxidative stress; basal ganglia siderosis; mitochondrial damage/mitophagy; and augmented GABAergic systems (increased GABA, GAD67 and reelin)...
June 28, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28743636/valproate-increases-dopamine-transporter-expression-through-histone-acetylation-and-enhanced-promoter-binding-of-nurr1
#16
Ashley L Green, Le Zhan, Aseel Eid, Helmut Zarbl, Grace L Guo, Jason R Richardson
The dopamine transporter (DAT) is the key regulator of dopaminergic transmission and is a target of several xenobiotics, including pesticides and pharmacological agents. Previously, we identified a prominent role for histone deacetylases in the regulation of DAT expression. Here, we utilized a rat dopaminergic cell line (N27) to probe the responsiveness of DAT mRNA expression to inhibitors of histone acetylation. Inhibition of histone deacetylases (HDACs) by valproate, butyrate and Trichostatin A led to a 3-10-fold increase in DAT mRNA expression, a 50% increase in protein levels, which were accompanied by increased H3 acetylation levels...
October 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28705346/efficient-generation-of-dopamine-neurons-by-synthetic-transcription-factor-mrnas
#17
Sang-Mi Kim, Mi-Sun Lim, Eun-Hye Lee, Sung Jun Jung, Hee Yong Chung, Chun-Hyung Kim, Chang-Hwan Park
Generation of functional dopamine (DA) neurons is an essential step for the development of effective cell therapy for Parkinson's disease (PD). The generation of DA neurons can be accomplished by overexpression of DA-inducible genes using virus- or DNA-based gene delivery methods. However, these gene delivery methods often cause chromosomal anomalies. In contrast, mRNA-based gene delivery avoids this problem and therefore is considered safe to use in the development of cell-based therapy. Thus, we used mRNA-based gene delivery method to generate safe DA neurons...
September 6, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28691794/ligand-dependent-switch-from-rxr-homo-to-rxr-nurr1-heterodimerization
#18
Marcel Scheepstra, Sebastian A Andrei, Rens M J M de Vries, Femke A Meijer, Jian-Nong Ma, Ethan S Burstein, Roger Olsson, Christian Ottmann, Lech-Gustav Milroy, Luc Brunsveld
Retinoid X receptors (RXRs) play key roles in many physiological processes in both the periphery and central nervous system. In addition, RXRs form heterodimers with other nuclear receptors to exert their physiological effects. The nuclear receptor related 1 protein (NURR1) is particularly interesting because of its role in promoting differentiation and survival of dopamine neurons. However, only a small number of RXR-heterodimer selective modulators are available, with limited chemical diversity. This work describes the synthesis, biochemical evaluation, and structural elucidation of a novel series of RXR ligands with strongly biased interactions with RXRα-NURR1 heterodimers...
September 20, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28685937/neuroimmunomodulatory-properties-of-dpscs-in-an-in-vitro-model-of-parkinson-s-disease
#19
Nareshwaran Gnanasegaran, Vijayendran Govindasamy, Vasudevan Mani, Noor Hayaty Abu Kasim
In neurodegenerative diseases, such as Alzheimer's and Parkinson's, microglial cell activation is thought to contribute to their degeneration by producing neurotoxic compounds. While dental pulp stem cells (DPSCs) have been regarded as the next possible cell source for cell replacement therapy (CRT), their actual role when exposed in such harsh environment remains elusive. In this study, the immunomodulatory behavior of DPSCs from human subjects was investigated in a coculture system consisting of neuron and microglia which were treated with 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine, which mimics the inflammatory conditions and contribute to degeneration of dopaminergic (DA-ergic) neurons...
September 2017: IUBMB Life
https://www.readbyqxmd.com/read/28607093/prostaglandin-e2-is-essential-for-efficacious-skeletal-muscle-stem-cell-function-augmenting-regeneration-and-strength
#20
Andrew T V Ho, Adelaida R Palla, Matthew R Blake, Nora D Yucel, Yu Xin Wang, Klas E G Magnusson, Colin A Holbrook, Peggy E Kraft, Scott L Delp, Helen M Blau
Skeletal muscles harbor quiescent muscle-specific stem cells (MuSCs) capable of tissue regeneration throughout life. Muscle injury precipitates a complex inflammatory response in which a multiplicity of cell types, cytokines, and growth factors participate. Here we show that Prostaglandin E2 (PGE2) is an inflammatory cytokine that directly targets MuSCs via the EP4 receptor, leading to MuSC expansion. An acute treatment with PGE2 suffices to robustly augment muscle regeneration by either endogenous or transplanted MuSCs...
June 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
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